The current study examined the relationship between demographic variables, treatment factors, and perceived barriers to care to both caregiver distress and caregiver-reported child health-related quality of life in caregivers of children diagnosed with cancer utilizing path analysis. Parental distress is examined as a potential mediator between barriers to care and income, as well as child age and caregiver-reported health-related quality of life (HRQOL). The final model demonstrated close fit to the data. Family income and perceived barriers to care demonstrated direct effects on caregiver distress. Child age, treatment intensity, severity of illness, and caregiver distress also demonstrated direct effects on caregiver-reported HRQOL. These results suggest a significant relationship between burden of care, caregiver functioning, and caregiver-reported child outcomes and support the transactional relationship between caregiver and child functioning.